methimazole and Cholestasis--Intrahepatic

Topics: Aged; Antithyroid Agents; Cholestasis, Intrahepatic; Humans; Hyperthyroidism; Male; Methimazole

We report a case of hepatotoxicity induced by methimazole treatment in a patient affected by hyperthyroidism. A 54-year-old man, presented to our observation for palpitations, excessive sweating, weakness, heat intolerance and weight loss. On physical examination, his blood pressure was 140/90 mmHg and heart beat was 100/min regular. He had mild tremors and left exophthalmos. Laboratory test revealed a significant increase in serum thyroid hormone levels with a decrease in thyroid stimulating hormone levels. A diagnosis of hyperthyroidism was made and he began treatment with methimazole (30 mg/day). Fourteen days later, he returned for the development of scleral icterus, followed by dark urine, and abdominal pain in the right upper quadrant. Laboratory examinations and liver biopsy performed a diagnosis of cholestatic hepatitis, secondary to methimazole usage. Methimazole was promptly withdrawn and cholestyramine, ursodeoxycholic acid, and chlorpheniramine were given. After five days, abdominal pain resolved and laboratory parameters returned to normal. Naranjo probability scale indicated a probable relationship between hepatotoxicity and methimazole therapy. In conclusion physicians should be aware the risk of hepatotoxicity related with methimazole.

Topics: Abdominal Pain; Antithyroid Agents; Biopsy; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Scleral Diseases

Hyperthyroidism is one of the most common endocrinology disorders. Treatment can be either pharmacological, surgical or using radioactive iodine. In Europe methimazole is the antithyroid drug of choice because it can be administered in a single daily dose and has a lower risk of adverse reactions. Around 5% of patients taking thionamides can present any of their side effects, which are usually mild. Liver toxicity due to thionamides is very rare, and severe due to propylthiouracil. We present a clinical case of a cholestatic jaundice and acute toxic hepatitis due to methimazole and a cross-reaction with propylthiouracil. Based on this case a review is presented.

Topics: Aged; Antithyroid Agents; Case Management; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Female; Graves Disease; Humans; Methimazole; Thyroidectomy

Drug-induced liver injury might be responsible for 1 of 600 to 3500 of all hospital admissions. About 2-3% of all drug adverse effects may be connected with the liver. There could be pure injury of heaptic cells or impairment of hepatocellular bile secretion. In our case there was cholestatic liver injury after the use of thiamazole with the complete regression after the discontinuation of the drug. For two years' the patient was treated with methyltiouracyl without any side effects. After 19 years, because of thyreotoxicosis, the methimazole was used. The acute cholestatic liver injury with the high serum bilirubin level (41.4 mg/dl) was observed. Despite the discontinuation of the drug the patient was deceased.. There are possible cross reactions among imidazolines in patients who are predispose to develop drug-induced liver failure. The doctors should pay much more attention to possible drug side effects.

Topics: Aged; Bilirubin; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Female; Humans; Hyperthyroidism; Liver Failure, Acute; Liver Function Tests; Methimazole; Treatment Outcome

A 28-year-old man presented with weight loss, jaundice, and pruritus. This was diagnosed to be secondary to Graves disease and the patient was prescribed methimazole. He returned 2 weeks later with worsening of his jaundice. Further investigation, including liver biopsy, indicated that there was superimposed methimazole-induced cholestasis. Discontinuation of methimazole and treatment of hyperthyroidism with lithium followed by radioactive iodine therapy resulted in resolution of his symptoms. This case highlights the fact that worsening cholestasis after therapy for Graves disease should raise the possibility of thionamide-induced exaggeration of liver cholestasis.

Topics: Adult; Antithyroid Agents; Cholestasis, Intrahepatic; Humans; Hyperthyroidism; Male; Methimazole

Cholestatic jaundice caused by imidazole derivates is a rare complication of antithyroid therapy. Only 20 such cases have been reported in the literature since the introduction of methimazole in 1949 and of carbimazole in 1953. We present a further case of methimazole-induced cholestatic liver injury, mimicking sclerosing cholangitis, where the etiology has been proven by a clear chronological relationship and the lack of other causative factors.

Topics: Adenoma; Aged; Antithyroid Agents; Bile Ducts, Intrahepatic; Chemical and Drug Induced Liver Injury; Cholangiopancreatography, Endoscopic Retrograde; Cholangitis, Sclerosing; Cholestasis, Intrahepatic; Diagnosis, Differential; Humans; Hyperthyroidism; Liver Function Tests; Male; Methimazole; Thyroid Neoplasms

The authors describe a 62 year-old white male who was diagnosed as autoimmune hyperthyroidism and treated with methimazole and atenolol. Ten days later he showed itching, jaundice and choluria. All drugs were discontinued. The patient was given radioactive iodine. Two months later direct serum bilirubin levels reached 35 mg%. Endoscopic retrograde cholangiogram evidenced normal extrahepatic biliary ducts. The percutaneous liver biopsy showed marked cholestasis specially in the centrolobular zone with a slight infiltrate of mononuclear cells in the portal areas. Together with the liver disease the patient presented an anemic syndrome. Bone marrow aspiration showed rich cellularity, Perls staining showed 70% sideroblasts, with 10% ringed sideroblasts and increased extracorpuscular iron. The patient's evolution was satisfactory. Twenty months after the beginning of the disease clinical and biochemical tests were normal. A new bone marrow aspiration rendered normal. Hepatic cholestasis suffered by our patient was probably due to an adverse reaction of methimazole. Physiopathology of reversible sideroblastic anemia is discussed.

Topics: Anemia, Sideroblastic; Atenolol; Cholestasis, Intrahepatic; Humans; Hyperthyroidism; Liver Function Tests; Male; Methimazole; Middle Aged; Thyroid Function Tests

The authors report a further case of methimazole-associated liver damage and present a brief review of eleven previous cases found in the literature. The main clinical features of this 58-year-old female patient were laboratory evidence of leucopenia and cholestasis, and biopsy features of fatty liver parenchyma degeneration with granulocytic portal infiltration and bile stasis, demonstrated 20 days after the initiation of antithyroid therapy with 20 mg methimazole daily. An immediate cholestatic liver reaction was also provoked by drug rechallenge, with spontaneous amelioration of signs and symptoms after drug discontinuation.

Topics: Cholestasis, Intrahepatic; Female; Humans; Hyperthyroidism; Liver; Methimazole; Middle Aged

Topics: Adult; Aged; Cholestasis, Intrahepatic; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Propranolol